Teeth and bones are a sole hard tissue in the body. Loss or defect in teeth and bones, which often occurs from fracture due to e.g., car accidents, results in morphological changes and/or functional disorder. In order to regenerate bone defect, there are being used various bone-grafting or bone-filling methods, using allograft, xenograft, metallic materials, polymer materials, ceramics, etc.
Materials supplementing the site of bone defects (conventionally, referred to as “bone-fillers”) are used for carrying out the bone-grafting or bone-filling methods. Recently, in order to reform legs for height-increase or reform dwarf jaws, osteogenesis is frequently performed, which results in increasing demand for bone-fillers.
Bio-materials incorporated into the human body as a bone-filler or a bone-grafting material may be classified into a bioinert material, a bioactive material, and a biodegradable material. The bio-inert material refers to a material neither inducing inflammation and toxicity nor binding to a biological tissue, when applied to a human body. The bioactive material refers to a material having high biocompatibility, which makes it possible to biochemically bind to adjacent tissues, when applied to a human body. The biodegradable material refers to a material absorbed or degraded in the body, after graft thereof. And also, the bio-materials may be classified into a metallic material, a ceramic material (i.e., an inorganic material), and a polymer material, according to a law material. The metallic material and the ceramic material are used mainly as a substitute for hard tissue such as teeth and bones. Recently, in order to utilize advantages of each material, a complex of ceramic and polymer or a mixture of metal and ceramic is occasionally used.
Metals have higher mechanical strength than ceramics and polymers. Stainless steel, an alloy of cobalt (Co) and chromium (Cr), titanium (Ti), titanium alloy (Ti-6Al-4V), a metallic mixture of titanium and nickel (1:1, atom ratio), etc. are used for a bone-filler or a bone-grafting material. Although metals are used mainly in a fine form, they are used in a porous metal form or in a metallic fiber form coated on a substitute surface, according to necessity. When metals in a porous metal form are grafted into a body, bone may be grown into the pores (small holes) of the substitute, which gives stronger binding between the bone and the substitute. And, metals or metallic fibers coated or adsorbed on a substitute surface provides concavo-convex forms on the surface, thereby enabling bone to grow into the gap, which gives high mechanical fixing effects.
Ceramic materials (i.e., inorganic materials) can provide superior chemical binding to bone, because the inorganic component of bones and teeth, i.e., apatite, is a ceramic material. Alumina and zirconia having good mechanical properties are used for bone-terminal and artificial tooth-root that require enduring abrasion. Bioactive ceramic materials include bioactive glasses having calcium oxide (CaO) and silicon dioxide (SiO2) as a main ingredient, and calcium phosphate ceramics having calcium and phosphorus that are major component of bone. Crystallized glasses of sodium oxide (Na2O)-calcium oxide-silicon dioxide are bioactive and have improved mechanical strengths such as flexural strength, fracture toughness, fatigue life, etc. Therefore, they are used for artificial spine, artificial ilium (hip bone), etc. Tricalcium phosphate (Ca3(PO4)2, TCP), composed of calcium and phosphorus similarly to apatite, has a continuously absorbed property, when grafted into a body. Therefore, it is widely used as a substitute material of hard tissues in the fields of orthopedics and orthodontics. Bioactive ceramics are appropriately used as bone fillers packing defected tooth or bones in a lump form. For this purpose, porous apatite, a complex of apatite and tricalcium phosphate, and a bioactive glass are mainly used as bone fillers. They are prepared conventionally in a 3-5 mm granular form, which is packed into defected sites of a bone. Bioactive ceramics may be used alone; be coated on metal surface for overcoming disadvantages of a metal substitute; or be used as injectable bone cements that fix a substitute by being injected in a cement form. The coating a metal substitute with bioactive ceramics can inhibit dissolution of metallic ions and also provide direct binding between the metal substitute and an adjacent bone without forming a fibrous coating layer. Currently, artificial hip joints coated with apatite or apatite and TCT are commercially available. And also, metallic screws or pins coated with bioactive ceramics are being introduced to markets.
Polymer materials include polylactic acid (PLA) or its copolymers and biodegradable polymers such as collagen. The polymer materials may be used for reducing modulus of elasticity, through mixing with metals or nonmetals (e.g., apatite).
Bone-grafting and bone-filling materials include an autologous bone, an allogeneic bone, a xenogenic bone, and said synthetic bones prepared with various bio materials. Among them, synthetic bones are mainly used, considering potential infection risk and economic issue. Hydroxyapatite is conventionally used as a main material of synthetic bones. Although hydroxyapatite has excellent osteoconductivity, it has low osteoinductivity. Therefore, when applied to a body, hydroxyapatite shows large deviation in bone-forming periods, according to patients' states and ages.
In order to overcome such disadvantages of synthetic bones, BMPs (bone morphogenic proteins) or other bone-grafting substitutes are used for inducing bone regeneration. For example, it has been reported that BMP2 facilitates fracture healing in a fracture-induced animal study (Welch, R. D. et al., J Bone Miner Res. 13(9):1483-1490, 1998; Yasko, A. W. et al., J Bone Joint Surg. 74A:659-671, 1992). On the basis of such research results, BMP2 was approved by the US FDA and is being used as a fracture-treating agent, a bone-grafting material, and a bone-filler, through applying to collagen sponge and various scaffolds. However, BMPs are very expensive and require using a large amount thereof. Therefore, because of high cost, the utilization of these proteins for bone-grafting or bone filling is limited.